When cardiomegaly is prolonged, the risk of heart failure, sudden death, and the like increases, and thus, it is important to suppress cardiomegaly in order to prevent and suppress heart failure. Such cardiomegaly is classified into those due to physiological conditions by exercise stress or the like, and those due to non-physiological conditions by pathological stress reaction of myocardium.
On the other hand, reactive oxygen (Reactive Oxygen Species: ROS) is known to participate in signal transduction of cell growth in many cells including those of the cardiovascular system. It is proved that reactive oxygen mediates the myocardial cell hypertrophy by angiotensin II and TNF-α in the myocardial cell, and it is shown that reactive oxygen participates in signal transduction of the myocardial cell hypertrophy as a second messenger (Non-Patent Literature 1). The relation between reactive oxygen and cardiomegaly is also reported at the cell level and the animal level, and it is known that reactive oxygen is promptly produced after stimulation by TNF-α, angiotensin II, endothelin-I or phenylephrine, which is a hypertrophy stimulator. In addition, sustained subcutaneous administration of angiotensin II is widely known as a cardiomegaly model, and it is known that reactive oxygen is also produced in the myocardium in this model.
Cardiomegaly, particularly cardiomegaly due to non-physiological conditions by pathological stress reaction of the myocardium is usually characterized by myocardial fibrosis and ventricular wall thickening. Persistent overstress to the myocardium by long term hypertension or abnormal stress to the myocardium after the myocardial infarction is often a cause for cardiomegaly. It is known that prolonged cardiomegaly leads to failure of the function of the heart as a pump, resulting in heart failure.
Statin, edaravone, β-blockers or the like is expected as a drug for such cardiomegaly, but the efficiency thereof has not been confirmed yet.
In addition, aneurysm is the most cause for subarachnoid hemorrhage, but the cause for the onset has not been clearly determined yet. Examples of a risk factor for aneurysm include hypertension and arteriosclerosis, but it is not clear whether they are a direct cause or not. As a therapeutic approach for aneurysm other than surgery, an antihypertensive drug is used only to prevent the progress thereof.